ANTISENSE PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE DOWN-REGULATION OF THE INSULIN-LIKE-GROWTH-FACTOR-I RECEPTOR IN OVARIAN-CANCER CELLS

The insulin-like growth factors (IGF-I and IGF-II) play a key role, in cellular proliferation and are involved in cellular transformation. T he expression of the IGF-I receptor has been demonstrated in a variety of human tumor cell lines including ovarian cancer cells. Phosphoroth ioate antisense oligodeoxynucleotides: (S-ODNs) were analyzed for thei r potential to suppress the IGF-I receptor in the NIH: OVCAR-3 ovarian cancer cell-line. The application of the antisense S-ON reduced;poten tly the cell growth of unstimulated NIH:OVCAR-3 cells; whereas sense a nd mismatch S-ODNs were without any effect. This effect resembled that of-the monoclonal antibody (MAb) alpha IR-3.ln contrast-to the antise nse compound, this MAb only partially inhibited the IGF-I-induced prol iferation of ovarian cancer cells. The concentration of the antisense S-ODN to exhibit an identical inhibition of cell proliferation was red uced to 50 nM when the oligonucleotides were delivered by the cationic lipid formulation lipofectin. The specificity of the antisense S-ODN action was confirmed by reduction of the receptor protein and of the r eceptor mRNA, as assayed by flow cytometry and by Northern blot hybrid izations. Our data demonstrate the potency of antisense S-ODNs to targ et the IGF-I receptor message and show that antisense strategies again st the IGF-I receptor may provide new strategies for the therapy of ov arian cancer. Int. J. Cancer 77:567-571, 1998. (C) 1998 Wiley-Liss, In c.